Temperature controlled crimping

ABSTRACT

This disclosure describes a method for crimping a stent with a polymer coating onto a catheter for percutaneous transluminal coronary angioplasty or other intraluminal interventions. The method comprises crimping the stent onto a catheter when the polymer coating is at a target temperature other than ambient temperature. The polymer coating can optionally comprise drug(s).

BACKGROUND

Percutaneous transluminal coronary angioplasty (PTCA) is a procedure fortreating heart disease. A surgeon introduces a catheter assembly havinga balloon portion percutaneously into the cardiovascular system of apatient via the brachial or femoral artery. The surgeon advances thecatheter assembly through the coronary vasculature until the balloonportion crosses the occlusive lesion. Once in position, the surgeoninflates the balloon to radially compress the atherosclerotic plaque ofthe lesion and remodel the vessel wall. The surgeon then deflates theballoon to remove the catheter.

An advance on PTCA involved using an intravascular stent. Mechanically,stents act as scaffoldings, physically holding open and, if desired,expanding the vessel wall. Typically, stents compress for insertionthrough small vessels and then expand to a larger diameter once inposition. U.S. Pat. No. 4,733,665, issued to Palmaz; U.S. Pat. No.4,800,882, issued to Gianturco; and U.S. Pat. No. 4,886,062, issued toWiktor disclose examples of PTCA stents.

Before this procedure can occur, equipment for the procedure must bemanufactured. Stent crimping is a critical step in manufacturing thisequipment in that stent retention depends on it. Generally, stentcrimping is the act of affixing the stent to the delivery catheter ordelivery balloon so that it remains affixed to the catheter or balloonuntil the physician desires to deliver the stent at the treatment site.Current stent crimping technology is sophisticated. A short time ago,one process used a roll crimper. This damaged many polymer coatings dueto its inherent shearing action. Next came the collet crimper; in it,metal jaws are mounted into what is essentially a drill chuck. The jawsmove in a purely radial direction. This movement was not expected toshear the coating, because it applied forces only normal to the stentsurface. But some stent geometries require that stent struts scissortogether during crimping. In those geometries, even if the crimperimposes only normal forces, the scissor action of the stent strutsimparts shear. Finally, the iris or sliding-wedge crimper imparts mostlynormal forces with some amount of tangential shear.

To use a roll crimper, first the stent is slid loosely onto the balloonportion of the catheter. This assembly is placed between the plates ofthe roll crimper. With an automated roll crimper, the plates cometogether and apply a specified amount of force. They then move back andforth a set distance in a direction that is perpendicular to thecatheter. The catheter rolls back and forth under this motion, and thediameter of the stent is reduced. The process can be broken down intomore than one step, each with its own level of force, translationaldistance, and number of cycles. With regard to a stent with a drugeluting coating, this process imparts a great deal of shear to the stentin a direction perpendicular to the catheter or catheter wall.Furthermore, as the stent is crimped, there is additional relativemotion between the stent surface and the crimping plates. As a result,this crimping process tends to damage the drug eluting stent coating.

The collet crimper is equally conceptually simple. A standarddrill-chuck collet is equipped with several pie-piece-shaped jaws. Thesejaws move in a radial direction as an outer ring is turned. To use thiscrimper, a stent is loosely placed onto the balloon portion of acatheter and inserted in the center space between the jaws. Turning theouter ring causes the jaws to move inward. An issue with this device isdetermining or designing the crimping endpoint. One scheme is toengineer the jaws so that when they completely close, they touch and acenter hole of a known diameter remains. Using this approach, turningthe collet onto the collet stops crimps the stent to the known outerdiameter. While this seems ideal, it can lead to problems. Stent strutshave a tolerance on their thickness. Additionally, the process offolding non-compliant balloons is not exactly reproducible.Consequently, the collet crimper exerts a different amount of force oneach stent in order to achieve the same final dimension. Unless thisforce, and the final crimped diameter, is carefully chosen, thevariability of the stent and balloon dimensions can yield stent coatingor balloon damage.

Furthermore, although the collet jaws move in a radial direction, theymove closer together as they crimp. This action, combined with thescissoring motion of the struts, imparts tangential shear on thecoatings that can also lead to damage. Lastly, the actual contactsurfaces of the collet crimper are the jaw tips. These surfaces arequite small, and only form a cylindrical surface at the final point ofcrimping. Before that point, the load being applied to the stent surfaceis discontinuous.

In the sliding wedge or iris crimper, adjacent pie-piece-shaped sectionsmove inward and twist, much like the leaves in a camera aperture. Thiscrimper can be engineered to have two different types of endpoints. Itcan stop at a final diameter, or it can apply a fixed force and allowthe final diameter to float. From the discussion on the collet crimper,there are advantages in applying a fixed level of force as variabilitiesin strut and balloon dimension will not change the crimping force. Thesliding wedges impart primarily normal forces, which are the leastdamaging to stent coatings. As the wedges slide over each other, theyimpart some tangential force. But the shear damage is frequently equalto or less than that of the collet crimper. Lastly, the sliding wedgecrimper presents a nearly cylindrical inner surface to the stent, evenas it crimps. This means the crimping loads are distributed over theentire outer surface of the stent.

All current stent crimping methods were developed for all-metal stents.Stent metals, such as stainless steel, are durable and can take abuse.When crimping was too severe, it usually damaged the underlying balloon,not the stent. But polymeric coatings present different challenges.

In the drug eluting stent arena, drugs are commonly placed on the stentin combination with a polymer. This placement typically coats all stentsurfaces. Then the stent is crimped onto the catheter. In general,polymer coatings are softer, weaker, and less durable than theunderlying stent material. Upon crimping with a sliding wedge crimper,and following crimp protocols for the particular stent, coating damageis frequently seen. FIGS. 1 and 2 show an Elasteon 80A (a polyurethane)coating on poly(ethylene-co-vinyl alcohol) (EVAL) after crimp, grip, andthe wet expansion test.

Grip is a process conducted after crimping to further increase stentretention. An outer sleeve restrains the crimped stent. Simultaneously,pressure and heat are applied to the stent-balloon section. Under thisaction, the balloon material deforms slightly, moving in between thestruts. In a wet expansion test, the final stent-on-catheter assembly isimmersed in deionized water at 37° C. for 30 seconds. Then the balloonis inflated according to the device instructions to at least a nominalpressure (8 atmospheres). After holding this pressure for 30 seconds,the balloon is deflated, and the stent slides off. After drying, thestent can be examined by optical microscopy or scanning electronmicroscopy for coating damage.

The primary purpose of the polymer in the stent coating is to containthe drug and control its release at a desired rate. Other obviousspecifications for the polymer are a high level of vascularbiocompatibility and the ability to flex and elongate to accommodatestent expansion without cracking or peeling. Meeting all of theseobjectives, while also possessing a high level of toughness and strengthto withstand conventional crimping process, can be challenging.

A crimping process that minimizes damage to the polymer coatings ofstents is needed.

SUMMARY

The current invention comprises several embodiments, some of whichrelate to extracorporeal methods of making medical devices orimplantable medical devices. These devices can comprise portions withcoatings. In some embodiments, the coating comprises a polymer orpolymer combination or drug(s). The piece comprising the coating iscrimped onto another part of the device or onto a separate device. Insome embodiments, crimping is done at non-ambient temperatures.Sometimes non-ambient-temperature crimping comprises changing thetemperatures of the coating, the piece comprising the coating, themedical device, the crimping device, or any combination of these.Likewise, medical devices made using these methods and devices forimplementing these methods are also part of this invention.

Specific heating and cooling profiles are used in different inventionembodiments. For instance, embodiments of crimping methods includeadjusting the temperature of the coating to a target temperaturefollowed by a crimping step; adjusting the temperature of the coating toa target temperature during a crimping step; adjusting the temperatureof the coating to a target temperature and maintaining the temperatureof the coating within plus or minus 5° C. of the target temperatureduring a crimping step; adjusting the temperature of the coating to atarget temperature followed by crimping such that the temperature of thecoating remains within plus or minus 10° C. of the target temperatureduring a crimping step; and adjusting the temperature of the coating toa temperature other than ambient towards a target temperature andcontinuing to adjust the temperature of the coating towards the targettemperature during a crimping step. Alternatively, the temperature ofthe coating can first be adjusted to a target temperature with thecrimper jaws then closing. After that, the temperature can be adjustedto a second temperature, followed by opening the crimper jaws.

Embodiments in which the target temperature takes values based on Tg andintervals around Tg are described, with the goal of some embodimentsbeing to simultaneously minimize deformation- and delamination-basedfailure during crimping. In some embodiments, the target temperatureultimately depends on the predominate failure mode of the polymercoating, Tg of the coating, shore D hardness of the polymer coating atambient temperature, and shore hardness of the polymer coating at thetarget temperature, among other factors.

In some embodiments, invention methods relate to making medical devicescomprising at least one coated piece wherein the coated piece cancomprise a coating. In some embodiments, the coating comprises a polymeror polymer combination and drug(s). A typical method comprises choosinga target temperature based on the mechanical behavior of the coatingmaterial, sometimes the behavior during crimping. The method furthercomprises juxtaposing the closing of the crimping jaws with adjustingthe temperature of the coating in any combination. For instance, thefollowing heating or cooling regimes are practical:

-   -   adjusting the temperature of the coating to a target temperature        followed by a crimping step;    -   adjusting the temperature of the coating to a target temperature        during a crimping step;    -   adjusting the temperature of the coating to a target temperature        and maintaining the temperature of the coating within plus or        minus 5° C. of the target temperature during a crimping step;    -   adjusting the temperature of the coating to a target temperature        followed by crimping such that the temperature of the coating        remains within plus or minus 10° C. of the target temperature        during a crimping step; and    -   adjusting the temperature of the coating to a temperature other        than ambient towards a target temperature and continuing to        adjust the temperature of the coating towards the target        temperature during a crimping step.

In these embodiments or others the heating or cooling regime cancomprise closing the crimper, adjusting the temperature of the coatingto a second temperature, and opening the crimper wherein the secondtemperature is greater than or less than the target temperature. Somemedical devices further comprise a catheter. In those devices, thecrimping step of invention methods can be used to attach the coatedpiece to the catheter.

Invention methods can be used on a variety of coating materialsincluding polymeric materials characterized as having Tg above or belowambient temperature. In some embodiments the methods act on coatingscomprising poly(ester amides); ABS resins; acrylic polymers and acryliccopolymers; acrylonitrile-styrene copolymers; alkyd resins; celluloseethers; celluloses; copoly(ether-esters); copolymers of polycarboxylicacids and poly-hydroxycarboxylic acids; copolymers of vinyl monomerswith each other and olefins; cyanoacrylates; epoxy resins; ethylenevinyl alcohol copolymer; ethylene-α-olefin copolymers; ethylene-methylmethacrylate copolymers; ethylene-vinyl acetate copolymers; poly(aminoacids); poly(anhydrides); poly(imino carbonates); poly(iminocarbonate);poly(orthoesters); poly(tyrosine arylates); poly(tyrosine derivecarbonates); polyacrylates; polyacrylic acid; polyacrylic acids;polyacrylonitrile; polyalkylene oxalates; polyamides; polyamino acids;polyanhydride; polyanhydrides; polycarbonates; polycarboxylic acids;polycyanoacrylates; polyesters; polyethers; poly-hydroxycarboxylicacids; polyimides; polyisobutylene and ethylene-α-olefin copolymers;polyketones; polymethacrylates; polyolefins; polyorthoester;polyorthoesters; polyoxymethylenes; polyphosphazenes; polyphosphoester;polyphosphoester urethane; polyphosphoesters;polyphosphoesters-urethane; polyurethane; polyurethanes;poly(ether-urethanes), poly(ester-urethanes), poly(silicone-urethanes),polyvinyl alcohol; polyvinyl aromatics; polyvinyl esters; polyvinylethers; polyvinyl ketones; poly(vinylidene fluoride), poly(vinylidenechloride), poly(vinylidene fluoride-co-hexafluoropropene),poly(vinylidene fluoride-co-chlorotrifluoroethylene), poly(vinylfluoride), poly(vinyl chloride), polyvinylidene halides; silicones;starches; vinyl copolymers vinyl-olefin copolymers; vinyl halidepolymers and copolymers; and vinyl halide polymers vinyl halide polymerscopolymers.

Specific examples of useful polymers for some embodiments include thefollowing polymers: starch, sodium alginate, rayon-triacetate, rayon,polyvinylidene fluoride, polyvinylidene chloride, polyvinyl pyrrolidone,polyvinyl methyl ether, polyvinyl chloride, polyvinyl acetate,polystyrene, polyisocyanate, polyisobutylene, polyethylene glycol,polydioxanone, polycaprolactone, polycaprolactam, polyacrylonitrile,poly(trimethylene carbonate), poly(L-lactic acid),poly(lactide-co-glycolide), poly(hydroxyvalerate),poly(hydroxybutyrate-co-valerate),poly(hydroxybutyrate-co-hydroxyvalerate), poly(hydroxybutyrate),poly(glycolide), poly(glycolic acid), poly(D,L-lactide-co-L-lactide),poly(D,L-lactide-co-glycolide), poly(D,L-lactide),poly(4-hydroxybutyrate), poly(3-hydroxybutyrate), poly(3-hydroxyvalerate), Nylon 66, hyaluronic acid, fibrinogen, fibrin,elastin-collagen, collagen, cellulose propionate, cellulose nitrate,cellulose butyrate, cellulose acetate butyrate, cellulose acetate,cellulose, cellophane, carboxymethyl cellulose, or poly(2-hydroxyethylmethacrylate).

Some invention methods operate on drug-containing coatings. In some ofthese embodiments, the drugs are selected from the following types:antiproliferative, antineoplastic, antiinflammatory, antiplatelet,anticoagulant, antifibrin, antithrombin, antimitotic, antibiotic,antioxidants, or their combinations.

The target temperature can be chosen in a number of ways. For instance,the target temperature can be

-   -   within or below the range defined by definition 1, definition 2,        definition 3, definition 4, definition 5, definition 6, or        definition 7 of the Tg range of the polymer or polymer        combination;    -   within or above the range defined by definition 1, definition 2,        definition 3, definition 4, definition 5, definition 6, or        definition 7 of the Tg range of the polymer or polymer        combination;    -   below ambient temperature;    -   below room temperature;    -   above ambient temperature;    -   above room temperature;    -   at or below −40° C.;    -   between ambient temperature and upper Tg of the Tg range;    -   between ambient temperature and lower Tg of the Tg range;    -   between −40° C. and upper Tg of the Tg range;    -   between −40° C. and lower Tg of the Tg range;    -   between −40° C. and ambient temperature;    -   at or above 80° C.;    -   between 80° C. and upper Tg of the Tg range;    -   between 80° C. and lower Tg of the Tg range; or    -   between 80° C. and ambient temperature.

Some invention embodiments choose the target temperature to avoidambient temperature or a window around ambient temperature. Otherembodiments choose the target temperature such that therapeutic agentspresent in the coating avoid substantial decomposition.

Some invention embodiments choose the target temperature tosimultaneously minimize deformation- and delamination-based failureduring crimping. Some invention embodiments choose the targettemperature to yield an improvement in shore hardness.

Different invention embodiments use a variety of methods for achievingthe temperature adjustment of the coating. For instance, the followingways of changing the temperature are all within the scope of the currentinvention:

-   -   contacting the coating or coated piece with a heat sink or heat        source.    -   directing a heated or cooled gas at the coating or coated piece;    -   placing the coating or coated piece near a heated or cooled        surface for emitting thermal or infrared radiation to or        absorbing thermal or infrared radiation from the coating or        coated piece;    -   placing the coating or coated piece near a heated or cooled        surface to enable convection to or from the coating or coated        piece to the surface;    -   heating or cooling the jaws of the crimper and thermally        contacting the coating or coated piece with the crimper jaws;    -   for crimper jaws that allow the passage of infrared radiation,        bathing the stent on catheter with infrared radiation;    -   heating the stent on catheter in an incubator or oven, or        cooling the stent on catheter in a refrigerator to        pre-equilibrate the stent on catheter to the desired temperature        before crimping.

For some invention devices useful in practicing invention methods, theheat sink or heat source is integrated with a crimping device. In someembodiments, the coated piece is selected from self-expandable stents,balloon-expandable stents, and stent-grafts.

BRIEF DESCRIPTION OF FIGURES

FIG. 1 shows a coating as prepared in Example 1, which is an Elasteon80A coating on EVAL after crimp, grip, and the wet expansion test.

FIG. 2 shows another coating as prepared in Example 1, which is Elasteon80A coating on EVAL after crimp, grip, and the wet expansion test.

FIG. 3 shows a topcoat of Solef 21508 on EVAL made using the proceduresof Example 3.

FIG. 4 shows another topcoat of Solef 21508 on EVAL, also made using theprocedures of Example 3.

FIG. 5 shows the tensile stress at yield of polypropylene as a functionof temperature.

FIG. 6 shows how the stress-strain curve of a thermoplastic polymerchanges with temperature.

FIG. 7 plots heat capacity versus temperature for a typicalthermoplastic polymer.

DETAILED DESCRIPTION

FIGS. 1 and 2 show that the coating on the outer surface of the stent,in one case, has been pinched or wrinkled over, while in the other, hasbeen smeared off. Similarly, FIGS. 3 and 4 show a topcoat of Solef 21508on EVAL. Solef 21508 is the softest poly(hexafluoropropene-co-vinylidenefluoride) thermoplastic polymer commercially available.

FIGS. 3 and 4 show dents in the high spots of the strut arms. Most highspots of these two stents show similar damage. For these reasons,polymer coatings made of lower durometer (80A for example) polymersfrequently fail quality assurance tests. EVAL, a hard plastic, seems tohold up to standard crimping, but it has a hardness of 85 shore D. Forcomparison, the low-density polyethylene used in milk containers is47-55 shore D.

A crimp process in which the coated stent is held at a targettemperature, which may be different from ambient, is disclosed. Atemperature below ambient can be used to increase polymer coatinghardness to avoid, shearing, tearing, pinching, and denting damage. Thisstrategy would be particularly effective for polymers with glasstransition temperatures (Tg) at or below ambient or temperature.Additionally, invention processes are suited for polymer mixtures inwhich the Tg of a polymer or polymer mixture is at or below ambienttemperature. Temperatures above ambient can be used in cases where theTg is above ambient or room temperature and greater coating ductility isdesired. For purposes of this disclosure, ambient temperature is thetemperature of the crimper or coating when the crimper or coating hasnot been purposely heated or cooled. Typically, this temperature will beclose to room temperature or the temperature surrounding the crimpingequipment or the coating. Similarly, for purposes of this disclosure, atarget temperature is a temperature numerically different from ambienttemperature brought about by purposely heating or cooling the crimper,stent, balloon, polymer coating, or any combination of these. Forpurposes of this disclosure, “polymer”, “polymer combination” and“polymer mixture” are synonymous, meaning a composition of one polymeror, when more than one polymer, a mixture of, a blend of, acopolymerization of, or any other combination of more than one polymer.The combination can occur after the more than one polymer waspolymerized or can occur during the polymerization of monomer into oneor more polymers. Durometer Temperature Temperature Hardness Range forRange for Polymer Tg ° C. Shore D Greater Hardness Ductility Solef 21508−29 60 −62 to 10   Ambient to 60 Elasteon 80A −100, 0 30-35 −110 to −10 Ambient to 60 Elasteon 55D −100, 0 55 −110 to −10  Ambient to 60EVAL-E151   55 85 Zero to Ambient 50 to 100 Kynar-Flex −30 65-70 −62 to10   Ambient to 60 2800 Butvar B-90 72-78 85-90 Zero to Ambient Ambientto 100 Kynar 710 −30 76-80 −62 to 10   Ambient to 60 Poly(n-butyl   20NA −30 to 15   Ambient to 60 methacrylate)

A representative method includes heating or cooling a polymer coating ona medical device to or towards a target temperature. Next, either afterthe target temperature has been reached or while the coating is changingtemperature towards the target temperature, the portion of the medialdevice containing the coating is crimped onto another portion of themedical device or onto another medical device. Crimping is done in atemperature region designed to minimize both cohesive and adhesivefailure (or deformation- and delamination-based failure) caused by localpressure from the jaws or surfaces of the crimping device, anddeformation of the stent caused by reducing its diameter. For instance,a polymer-coated stent can be heated with a stream of air and crimpedonto a delivery catheter with an iris crimper.

Heating and cooling are generically discussed as “adjusting” thetemperature of the coating, the crimper, or the medical device.Adjusting the temperature comprises placing the object that is to haveits temperature adjusted into thermal contact with a heat sink or heatsource. For purposes of this disclosure, thermal contact with a heatsink means heat sink arrangement vis a vis the object so that energywould flow or be carried from the object to the heat sink. For purposesof this disclosure, thermal contact with a heat source means heat sourcearrangement vis a vis the object so that energy would flow or be carriedfrom the heat source to the object. Thermal contact is a generic term atleast encompassing an arrangement of the object such that radiation,conduction, or convection to or from the heat sink or heat source wouldtransfer energy. In some embodiments, thermal contact is defined toexclude any of radiation, conduction, convection, or any combination ofthese.

Different invention embodiments employ different heating or coolingprofiles. For instance, when the heating profile calls for softening thepolymer by choosing a target temperature above some temperature value,the coating is adjusted to the target temperature before crimping andthen crimping occurs (with or without some amount of cooling beforecrimping); alternatively, the coating is adjusted to the targettemperature before crimping and maintained at or near the targettemperature during crimping; alternatively, crimping is started, thecoating is adjusted to the target temperature, and crimping iscompleted. For purposes of this disclosure, “maintained near the targettemperature” means that the temperature of the coating at the instant ofcontact with the crimper is the target temperature plus or minus 20° C.,15° C., 10° C., 5° C., 2° C. or 1° C. In some embodiments, “maintainednear the target temperature” means that the temperature of the coatingat the instant of contact with the crimper is the target temperatureplus or minus 10° C.

Similarly, if a cooling profile calls for hardening a polymer bychoosing a target temperature below some temperature value, the coatingis adjusted to the target temperature before crimping and then crimpingoccurs (with or without some amount of warming before crimping);alternatively, the coating is adjusted to the target temperature beforecrimping and maintained at or near the target temperature duringcrimping; alternatively, crimping is started, the coating is adjusted tobe target temperature, and crimping is completed.

Polymers on crimped stents exhibit adhesive and cohesive failure as twomain failure modes. In adhesive failure, the coating is sheared off thestent due to poor adhesion to the metal stent or underlying polymerlayers. This is a failure of the polymer layer due to poor interactionbetween polymer molecules and the surface of the stent. Since at highertemperatures, particularly those above Tg, polymeric materials aresofter, a higher temperature crimp process could assist in preventingadhesive failure at the polymer-stent surface interface. Adhesivefailure is sometimes referred to as an adhesive-based failure ordelamination-based failure. When a polymer coating on a stent exhibitsadhesive failure, that polymer becomes a candidate for crimping above Tgof the polymer. Adhesive failure is also caused by a build-up of stressat the polymer-metal interface. Heating the polymer above its Tg lowersits modulus and decreases the stress build-up at the interface. Whenstents are crimped, certain portions of the stent pattern undergoelongation. If this degree of elongation exceeds the elongation of thecoating, the coating will crack. The ultimate elongation of polymers isa temperature function, and heating the polymer above its Tg canincrease the ultimate elongation, thereby preventing coating failure. Ifthe polymer coating exhibits a cohesive failure due to insufficientelongation, it is also a candidate for crimping above the Tg of thepolymer.

In cohesive failure, the topmost polymer layer is mechanically dented,deformed, or torn. This is a failure of the polymer layer due to poorinteraction between polymer molecules. Since at lower temperatures,particularly those below Tg, polymeric materials are harder, a lowtemperature crimp process can be suited to preventing cohesive damage tothe polymer surface. Cohesive failure is sometimes referred to as acohesive-based failure or a deformation-based failure. When a polymercoating on the stent exhibits cohesive failure due to compressive loads,that polymer becomes a candidate for crimping below Tg of the polymer.

FIG. 5 shows tensile stress at yield of polypropylene as a function oftemperature. This property is not the same as hardness, but correlateswith it. Both involve the stress needed to permanently deform thepolymer. For thermoplastics in general, a lower temperature leads togreater hardness. FIG. 6 shows how a thermoplastic's stress-strain curvechanges with temperature.

For some embodiments of this invention, the target temperature isselected in relation to Tg of the coating. Tg is the temperature atwhich the amorphous domains of a polymer change from a brittle vitreousstate to a plastic state at atmospheric pressure. In other words, Tgcorresponds to the temperature where the onset of segmental motion inthe chains of the polymer occurs, and it is discernible in aheat-capacity-versus-temperature graph for a polymer, as is depicted inFIG. 7. When an amorphous or semicrystalline polymer is heated, itscoefficient of expansion and heat capacity both increase as thetemperature rises, indicating increased molecular motion. As thetemperature rises, the sample's actual molecular volume remainsconstant. Therefore, a higher coefficient of expansion points to a freevolume increase of the system and increased freedom of movement for themolecules. The increasing heat capacity corresponds to increasing heatdissipation through movement.

Tg of a given polymer can be dependent on the heating rate and can beinfluenced by the thermal history of the polymer. Furthermore, polymerchemical structure heavily influences Tg by affecting polymer mobility.Generally, flexible main-chain components lower Tg and bulky side groupsraise Tg. Similarly, increasing flexible-side-group length lowers Tg andincreasing main-chain polarity increases Tg. Additionally, the presenceof crosslinks can increase the observed Tg for a given polymer, and thepresence of a drug or therapeutic agent can alter the Tg of a polymerdue to plasticization effects. The magnitude of these plasticizationeffects depends on the miscibility and compatibility of the drug andpolymer and the loading of drug in the polymer.

By way of illustration, when a semicrystalline polymer is heated, thepolymer crystallinity begins to increase as temperature reaches Tg. Ator above Tg, the increased molecular motion allows the polymer chains toadopt a more thermodynamically stable relationship, and therebyincreases polymer crystallinity. In FIG. 7, Tg is shown on the firstcurve, 60, which is the temperature at which half of the increase inheat capacity has occurred. The crystallinity then increases rapidlyafter Tg and reaches a maximum at Tc (the apex of second curve, 62).

As can be seen in FIG. 7, Tg is somewhat arbitrarily placed on thetemperature versus heat capacity curve. For purposes of this disclosure,the Tg range is defined in several different ways for a polymer orpolymer combination. Some invention embodiments can be predicated on anyone of these Tg range definitions.

Tg Range Definition 1

For this definition, Tg range is greater than or equal to the initialpoint on the polymer's (or polymer combination's)temperature-versus-heat-capacity curve showing a drop in heat capacity,indicated as Tg1 (100) on FIG. 7 (this point is defined as lower Tg fordefinition 1). Tg range is less than or equal to Tc (110) on the curvein FIG. 7 (this point is defined as upper Tg for definition 1). This Tgrange is referred to in this disclosure as Tg range definition 1. Thoseof ordinary skill in the art recognize that the specific curvature andtemperature points in FIG. 7 depend upon the nature of the polymer orpolymer combination. Therefore, the indication of a point on FIG. 7 ismeant to communicate a point corresponding to the FIG. 7 point on asimilar graph for the particular polymer or polymer combination beingused.

A target temperature is within Tg range definition 1 if it is above orequal to Tg1 and below or equal to Tg2. A target temperature is below Tgrange definition 1 if it is below or equal to Tg2. A target temperatureis above Tg range definition 1 if it is above or equal to Tg1. A targettemperature is between a higher temperature and a lower temperature ifit is above or equal to the lower temperature and below or equal to thehigher temperature. These concepts hold for all temperatures and rangesthroughout this disclosure.

Tg Range Definition 2

For this definition, the Tg range is greater than or equal to the pointTg1 (100) on FIG. 7 (lower Tg for definition 2) and less than or equalto point 140 on FIG. 7 (upper Tg for definition 2). This range isreferred to in this disclosure as Tg range definition 2. Point 140corresponds to the onset of the crystallization phase transition for thematerial.

Tg Range Definitions 3, 4, 5, and 6

For definition 3, the Tg range is the conventionally measured Tg (180)for the polymer (or combination) plus 40° C. (upper Tg for definition 3)and minus 40° C. (lower Tg for definition 3).

For definition 4, the Tg range is the conventionally measured Tg for thepolymer (or combination) plus 20° C. (upper Tg for definition 4) and−20° C. (lower Tg for definition 4).

For definition 5, the Tg range is the conventionally measured Tg for thepolymer (or combination) plus 10° C. (upper Tg for definition 5) andminus 10° C. (lower Tg for definition 5).

For definition 6, the Tg range is the conventionally measured Tg for thepolymer (or combination) plus 5° C. (upper Tg for definition 6) andminus 5° C. (lower Tg for definition 6).

Tg Range Definition 7

For this definition, the Tg range is greater than or equal to the pointTg1 (100) on FIG. 7 (lower Tg for definition 7) and less than or equalto point 160 on FIG. 7 (upper Tg for definition 7). This range isreferred to in this disclosure as Tg range definition 7. Point 160corresponds to the tail off or end of the glass phase transition for thematerial.

These embodiments also include embodiments in which the Tg rangespecifically excludes ambient temperature, ambient temperature + or −1°C. or ambient temperature + or −5° C. Also, in some embodiments thetarget temperature has a maximum at or below the temperature at whichany included therapeutic agents substantially decompose. For purposes ofthis disclosure, “substantially decompose” means decomposition to theextent that one of ordinary skill in the art would conclude that thedecomposition would reduce the efficacy of the therapeutic substance toomuch. In other words, decomposition would reduce the efficacy enoughthat one of ordinary skill in the art would reject the heated or cooled,crimped composition for use in vivo.

Based on the shore hardness of the coating or the failure mode of thecoating, several embodiments can be described. For coatings that are toosoft, that exhibit cohesive or deformation failures, that have Tg belowambient or room temperature, or that have a shore hardness of shore 60Ato 80D (alternatively, shore 80A to 60D), the polymer can be improved bycausing the polymer to be harder during crimping. This can beaccomplished by choosing a target temperature less than upper Tg. (Whenthis disclosure speaks of upper Tg or lower Tg, but does not specifywhich definition of Tg range is being used, this disclosure is intendedto cover upper and lower Tg for each range definition). Alternatively,the polymer can be hardened during crimping by choosing a targettemperature below lower Tg. Alternatively, choosing a target temperaturebelow ambient temperature can harden the polymer. Alternatively,choosing a target temperature below −30° C., −40° C., −50° C., or −60°C. can harden the polymer. In some embodiments, the target temperatureis between ambient temperature and upper Tg; ambient temperature andlower Tg; or −30° C., −40° C., −50° C., or −60° C. and upper Tg; −30°C., −40° C., −50° C., or −60° C. and lower Tg; or −30° C., −40° C., −50°C., or −60° C. and ambient temperature.

In addition to choosing the target temperature based on the Tg rangedefinitions discussed above, various embodiments can be describedotherwise. For coatings that are too soft, that exhibit cohesive ordeformation failures, that have Tg below ambient or room temperature, orthat have a shore hardness of shore 60A to 80D (alternatively, shore 80Ato 60D), the polymer can be improved by causing the polymer to be harderduring crimping. Therefore, an improvement in cohesive or deformationfailures can be achieved by choosing a target temperature that yields a50% increase in shore hardness, alternatively, a 40%, 30%, 20%, or 10%increase in shore hardness.

Medical devices that use outermost coatings with shore hardness of shore60A to 60D frequently experience cohesive failure during crimping.Invention medical devices prepared with invention crimping methods allowthe use of outermost coatings with shore D hardness as low as 30 to 80,or 35 to 60. Alternatively, invention medical devices prepared withinvention crimping methods allow the use of outermost coatings withshore D hardness less than or equal to 45, 40, 35, or 30.

For coatings that are too hard, that exhibit adhesive failures, haveinsufficient elongation, or that have Tg above ambient or roomtemperature, or that have a shore hardness of 60D to 95D (alternatively,65D to 90D), the polymer can be improved by causing the polymer to besofter during crimping. This can be accomplished by choosing a targettemperature greater than upper Tg. Alternatively, the polymer can besoftened during crimping by choosing a target temperature above lowerTg. Alternatively, choosing a target temperature above ambienttemperature can soften the polymer. Alternatively, choosing a targettemperature above 70° C., 80° C., 90° C., or 100° C. can soften thepolymer. In some embodiments, the target temperature is between ambienttemperature and upper Tg; ambient temperature and lower Tg; between 70°C., 80° C., 90° C., or 100° C. and upper Tg; between 70° C., 80° C., 90°C., or 100° C. and lower Tg; or between 70° C., 80° C., 90° C., or 100°C. and ambient temperature.

In addition to choosing the target temperature based on the Tg rangedefinitions discussed above, various embodiments can be describedotherwise. For coatings that are too hard, that exhibit adhesivefailures, that have Tg above ambient or room temperature, or that have ashore hardness of 60D to 95D (alternatively, 65D to 90D), the polymercan be improved by causing the polymer to be softer during crimping.Therefore, an improvement in adhesive failure can be achieved bychoosing a target temperature that yields a 50% decrease in shorehardness, alternatively, a 40%, 30%, 20%, or 10% decrease in shorehardness.

Medical devices that use outermost coatings with shore hardness of shore60D to shore 90D frequently experience adhesive, or elongational failureduring crimping. Invention medical devices prepared with inventioncrimping methods allow the use of outermost coatings with shore hardnessas high as 60D to 90D, or 65D to 85D. Alternatively, invention medicaldevices prepared with invention crimping methods allow the use ofoutermost coatings with shore hardness greater than or equal to 60D,70D, 80D, or 90D.

When EVAL is crimped at ambient temperature, it is in a glassy state(FIG. 6, curve A). By crimping at a temperature above its glasstransition temperature (Tg) (55° C.), the ultimate elongation becomeshigher (FIG. 6, curve B). This should reduce cracking in the tensileregions on the outside of stent junctions. For PBMA, Tg of 20° C.,crimping at a low temperature of 0° or less should reduce crimpingdamage from shear and compression. Similarly, for KYNAR (a polymerconsisting of poly(vinylidene fluoride) and available from Atofina ofPhiladelphia, Pa.), Tg of −30° C., crimping at a temperature of −40° C.should also reduce denting and shearing damage.

Devices for crimping medical devices are well known in the art. In someembodiments, the device is designed to crimp the polymer-coated stentonto the balloon portion of a catheter for PTCA. For crimpers such asthe sliding wedge design, the temperature may be controlled by passageof a stream of dry air, or inert gas through the bore. This air can beheated or cooled by first passing it through a tube heater or chilledheat exchanger. The stent is loosely placed onto the catheter, and thenthe assembly is inserted into the bore of the crimper. The passage ofair would rapidly equilibrate the stent delivery system (SDS) to thecrimp temperature. Continuously heated or cooled airflow would bring thecrimping jaws to the desired temperature.

Alternative ways include heating or cooling the jaws of the crimperitself. Electrical heating elements can be installed into the crimperjaws. By appropriate placement of thermocouples and feedback controls,an elevated temperature can be maintained. Cooling of the crimper jawscan be accomplished by rendering them with passageways through which acooling medium is pumped. This may also be used to heat the crimpingjaws. If the jaws were composed of an electrically conductive material,application of an oscillating electric field can heat them via eddycurrents. If the jaws were made of an IR transparent material, the stenton catheter can be thermostated by infrared radiation.

If the crimper is at ambient temperature, but the jaws themselves are ofa material with low thermal conductivity, then processes can beconsidered where the stent loosely applied to the catheter ispre-equilibrated to a non-ambient temperature before crimping. As theDES system is small, with a high surface area to volume ratio, the DESsystem would have to be rapidly moved from the controlled temperatureenvironment to the crimper to maintain the desired temperature. Heatingin an incubator or oven, or cooling in a refrigerator canpre-equilibrate the DES system to the desired temperature beforecrimping.

Processes of the current invention provide medical devices. Thesemedical devices contain a piece or portion that is coated, in someembodiments, with polymer(s). In some embodiments, the crimping deviceused in invention crimping steps can be heated or cooled before it isused to crimp the coated piece or portion onto the remainder of themedical device or onto another medical device. This heating or coolingcauses the temperature of the coating material to change so that thecrimping effectively occurs at a target temperature other than ambienttemperature. Other ways of modifying the temperature of the coatinginclude heating or cooling the substrate of the medical device orheating or cooling the coating directly with forced air, among othermethods.

Some invention embodiments select medical devices to be those adaptedfor placement in arterial, venous, neurovascular, urethral, biliary,prostate, intravascular, ureteral, bronchial, esophageal, fallopial,tracheal, laryngeal, gastrointestinal, lymphatic, eustachiaic,pancreatic, cerebral, other genitourinary, other gastrointestinal, orother respiratory lumens or passages.

Representative examples of polymer families that can be used to coat amedical device in accordance with the present invention includepoly(ester amides); ABS resins; acrylic polymers and acrylic copolymers;acrylonitrile-styrene copolymers; alkyd resins; cellulose ethers;celluloses; copoly(ether-esters) (e.g. PEO/PLA); copolymers ofpolycarboxylic acids and poly-hydroxycarboxylic acids; copolymers ofvinyl monomers with each other and olefins; cyanoacrylates; epoxyresins; ethylene vinyl alcohol copolymer; ethylene-α-olefin copolymers;ethylene-methyl methacrylate copolymers; ethylene-vinyl acetatecopolymers; poly(amino acids); poly(anhydrides); poly(imino carbonates);poly(orthoesters); poly(tyrosine arylates); poly(tyrosine derivecarbonates); polyacrylates; polyacrylic acid; polyacrylic acids;polyacrylonitrile; polyalkylene oxalates; polyamides; polyamino acids;polyanhydride; polyanhydrides; polycarbonates; polycarboxylic acids;polycyanoacrylates; (mentioned above); polyesters; polyethers;poly-hydroxycarboxylic acids; polyimides; polyisobutylene andethylene-α-olefin copolymers; polyketones; polymethacrylates;polyolefins; polyorthoester; polyorthoesters; polyoxymethylenes;polyphosphazenes; polyphosphoester; polyphosphoester urethane;polyphosphoesters; polyphosphoesters-urethane; poly(ether-urethanes),poly(ester-urethanes), poly(silicone-urethanes), polyurethane;polyurethanes; polyvinyl alcohol; polyvinyl aromatics; polyvinyl esters;polyvinyl ethers; polyvinyl ketones; poly(vinylidene fluoride),poly(vinylidene chloride), poly(vinylidenefluoride-co-hexafluoropropene), poly(vinylidenefluoride-co-chlorotrifluoroethylene), poly(vinyl fluoride), poly(vinylchloride), polyvinylidene halides; silicones; starches; vinyl copolymersvinyl-olefin copolymers; vinyl halide polymers and copolymers; and vinylhalide polymers vinyl halide polymers copolymers.

Representative examples of polymers that can be used to coat a medicaldevice in accordance with the present invention include starch, sodiumalginate, rayon-triacetate, rayon, polyvinylidene fluoride,polyvinylidene chloride, polyvinyl pyrrolidone, poly(iminocarbonate),polyvinyl methyl ether, polyvinyl chloride, polyvinyl acetate,polystyrene, polyisocyanate, polyisobutylene, polyethylene glycol,polydioxanone, polycaprolactone, polycaprolactam, polyacrylonitrile,poly(trimethylene carbonate), poly(L-lactic acid),poly(lactide-co-glycolide), poly(hydroxyvalerate),poly(hydroxybutyrate-co-valerate),poly(hydroxybutyrate-co-hydroxyvalerate), poly(hydroxybutyrate),poly(glycolide), poly(glycolic acid), poly(D,L-lactide-co-L-lactide),poly(D,L-lactide-co-glycolide), poly(D,L-lactide),poly(4-hydroxybutyrate), poly(3-hydroxybutyrate), poly(3-hydroxyvalerate), Nylon 66, hyaluronic acid, fibrinogen, fibrin,elastin-collagen, collagen, cellulose propionate, cellulose nitrate,cellulose butyrate, cellulose acetate butyrate, cellulose acetate,cellulose, cellophane, carboxymethyl cellulose, and 2-hydroxyethylmethacrylate.

The polymer coating for use with this invention can comprise a mixtureof polymers, such as an intimate mixture of polymer molecules, or canuse a combination of polymers arranged in a layered structure. One ofordinary skill in the art will recognize that the optimal targettemperature can be chosen based on the overall thermal behavior of thepolymers or combination of polymers.

In some embodiments, the crimping process operates on polymers ormixtures of polymers comprising a drug that can inhibit vascular smoothmuscle cell activity. More specifically, the drug activity can aim atinhibiting abnormal or inappropriate migration or proliferation ofsmooth muscle cells to prevent, inhibit, reduce, or treat restenosis.The drug can also include any substance capable of exerting atherapeutic or prophylactic effect in the practice of the presentinvention. Examples of such active agents include antiproliferative,antineoplastic, antiinflammatory, antiplatelet, anticoagulant,antifibrin, antithrombin, antimitotic, antibiotic, and antioxidantsubstances as well as their combinations. An example of anantiproliferative substance is actinomycin D, or derivatives and analogsthereof (manufactured by Sigma-Aldrich 1001 West Saint Paul Avenue,Milwaukee, Wis. 53233; or COSMEGEN available from Merck). Synonyms ofactinomycin D include dactinomycin, actinomycin IV, actinomycin I1,actinomycin X1, and actinomycin C1. Examples of antineoplastics includepaclitaxel and docetaxel. Examples of antiplatelets, anticoagulants,antifibrins, and antithrombins include aspirin, sodium heparin, lowmolecular weight heparin, hirudin, argatroban, forskolin, vapiprost,prostacyclin and prostacyclin analogs, dextran,D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole,glycoprotein IIb/IIIa platelet membrane receptor antagonist, recombinanthirudin, thrombin inhibitor (available from Biogen), and 7E-3B® (anantiplatelet drug from Centocor). Examples of antimitotic agents includemethotrexate, azathioprine, vincristine, vinblastine, fluorouracil,Adriamycin, and mutamycin. Examples of cytostatic or antiproliferativeagents include angiopeptin (a somatostatin analog from Ibsen),angiotensin converting enzyme inhibitors such as Captopril (availablefrom Squibb), Cilazapril (available from Hoffman-LaRoche), or Lisinopril(available from Merck & Co., Whitehouse Station, N.J.), calcium channelblockers (such as Nifedipine), colchicine, fibroblast growth factor(FGF) antagonists, histamine antagonist, Lovastatin (an inhibitor ofHMG-CoA reductase, a cholesterol lowering drug from Merck & Co.),monoclonal antibodies (such as PDGF receptors), nitroprusside,phosphodiesterase inhibitors, prostaglandin inhibitor (available fromGlazo), Seramin (a PDGF antagonist), serotonin blockers, thioproteaseinhibitors, triazolopyrimidine (a PDGF antagonist), and nitric oxide.Other useful drugs may include alpha-interferon, genetically engineeredepithelial cells, dexamethasone, estradiol, clobetasol propionate,cisplatin, insulin sensitizers, receptor tyrosine kinase inhibitors, andcarboplatin. Exposure of the composition to the drug should notadversely alter the drug's composition or characteristic. Accordingly,drug-containing embodiments choose drugs that are compatible with theblended composition. Rapamycin is a suitable drug. Additionally,40-O-(2-hydroxy)ethyl-rapamycin, or a functional analog or structuralderivative thereof, is suitable, as well. Examples of analogs orderivatives of 40-O-(2-hydroxy)ethyl-rapamycin include, among others,40-O-(3-hydroxy)propyl-rapamycin and40-O-2-(2-hydroxy)ethoxyethyl-rapamycin. Those of ordinary skill in theart know of various methods and coatings for advantageously controllingthe release rate of drugs, such as 40-O-(2-hydroxy)ethyl-rapamycin.

Some embodiments choose the drug such that it does not contain at leastone of or any combination of antiproliferative, antineoplastic,antiinflammatory, antiplatelet, anticoagulant, antifibrin, antithrombin,antimitotic, antibiotic, or antioxidant substances. Some inventionembodiments choose the drug such that it does not contain at least oneof or any combination of actinomycin D, derivatives and analogs ofActinomycin D, dactinomycin, actinomycin IV, actinomycin I1, actinomycinX1, actinomycin C1, paclitaxel, docetaxel, aspirin, sodium heparin, lowmolecular weight heparin, hirudin, argatroban, forskolin, vapiprost,prostacyclin, prostacyclin analogs, dextran,D-phe-pro-arg-chloromethylketone (synthetic antithrombin), dipyridamole,glycoprotein IIb/IIIa platelet membrane receptor antagonist, recombinanthirudin, thrombin inhibitor and 7E-3B, methotrexate, azathioprine,vincristine, vinblastine, fluorouracil, adriamycin, mutamycin,angiopeptin, angiotensin converting enzyme inhibitors, Captopril,Cilazapril, or Lisinopril, calcium channel blockers, Nifedipine,colchicine, fibroblast growth factor (FGF) antagonists, histamineantagonist, Lovastatin, monoclonal antibodies, PDGF receptors,nitroprusside, phosphodiesterase inhibitors, prostaglandin inhibitor,Seramin, PDGF antagonists, serotonin blockers, thioprotease inhibitors,triazolopyrimidine, nitric oxide, alpha-interferon, geneticallyengineered epithelial cells, dexamethasone, estradiol, clobetasolpropionate, cisplatin, insulin sensitizers, receptor tyrosine kinaseinhibitors, carboplatin, Rapamycin, 40-O-(2-hydroxy)ethyl-rapamycin, ora functional analogs of 40-O-(2-hydroxy)ethyl-rapamycin, structuralderivative of 40-O-(2-hydroxy)ethyl-rapamycin,40-O-(3-hydroxy)propyl-rapamycin, and40-O-2-(2-hydroxy)ethoxyethyl-rapamycin.

Some embodiments comprise polymers combined with other polymers inmultilayer arrangements. For example, one polymer can under- or over-layanother polymer such as a polymer coated on a device, a medical device,an implantable medical device, or a stent. The polymer can be used neatin this regard, or it can first be mixed with another polymer.

Examples of implantable devices useful in the present invention includeself-expandable stents, balloon-expandable stents, and stent-grafts. Theunderlying structure of the device can be of virtually any design. Thedevice can comprise a metallic material or an alloy such as, but notlimited to, cobalt chromium alloy (ELGILOY), stainless steel (316L),high nitrogen stainless steel, e.g., BIODUR 108, cobalt chrome alloyL-605, “MP35N,” “MP20N,” ELASTINITE (Nitinol), tantalum, nickel-titaniumalloy, platinum-iridium alloy, gold, magnesium, or combinations thereof.“MP35N” and “MP20N” are trade names for alloys of cobalt, nickel,chromium, and molybdenum available from Standard Press Steel Co.,Jenkintown, Pa. “MP35N” consists of 35% cobalt, 35% nickel, 20%chromium, and 10% molybdenum. “MP20N” consists of 50% cobalt, 20%nickel, 20% chromium, and 10% molybdenum. Of course, one of ordinaryskill in the art recognizes that the invention method is only useful formedical devices that use a crimping step in their production.

Various, specialized tests are used to assay the integrity of a drugeluting stent coating. In all of them, completed units are tested whichhave been though all stent-catheter assembly processes, includingcrimping and any heat-pressure processes. One test is inspection of thecoated stents by scanning electron microscopy. This can be done on thecompleted units by cutting the stent-balloon section from the catheter,or the stent can be removed from the catheter by dry expansion in air orwet expansion in aqueous solution. Under SEM, the fraction ofcompromised coating surface area can be estimated. Compromised coatingis coating that has been deformed, torn, or removed. When this fractionof surface area exceeds 5-10%, the drug-release-rate properties, andtotal drug content can be affected. Another measure of coatingintegrity, which is tied to crimping damage, is the number and size ofparticles shed when the stent is expanded in aqueous solution. The stentis deployed in a solution of previously filtered water and the particlesshed are counted by one of several available particle-countinginstruments. Example instruments would be those produced by Malvern thatwork by light scattering, instruments that work by light obscuration,such as the Hiac-Royco, or the Coulter counter which works by electricalconductivity. Elevated numbers, and sizes, of particles shed areindicative of coating failure, which is affected by crimping damageeither in the form of coating pieces that are completely shorn off, orcracks in the coating which propagated during stent expansion toliberate particles. Yet another approach to measuring the effects ofcoating crimping damage is by acute thrombogenicity testing, one exampleof which is that detailed by Sukavaneshvar et al. ASAIO Journal, Aug.11, 2000, p 301 and ASIAO Journal, Jul. 5, 2000, p M393, which approachsubjected stents deployed in tubing to a flow of bovine blood in whichthe platelets have been radiolabeled. Accumulation of platelets andthrombus is a measure of the acute thrombogenicity. The effect ofcoating cracks and defect can be compared to uncoated stents, or tostents where the coatings have fewer, or no cracks and coating defects.

EXAMPLES Example 1 Used to Make Stents for FIGS. 1 & 2

A first composition was prepared by mixing the following components:

-   (a) 2.0 mass % of poly(ethylene-co-vinyl alcohol) (EVAL) EC-151A and-   (b) the balance, dimethylacetamide

The first composition was applied onto the surface of bare 13 mm TETRAstents (available from Guidant Corporation), which were firstpre-expanded by passing them over a 0.071 inch, tapered mandrel. Coatingwas sprayed and dried to form a primer layer. A spray coater was usedhaving a 0.046 fan nozzle maintained at about 60C with a feed pressure2.5 psi (0.17 atm) and an atomization pressure of about 15 psi (1.02atm). Coating was applied at 10 μg per pass, in between which the stentwas dried for 10 seconds in a flowing air stream at 60C. Approximately70 μg of wet coating was applied. The stents were baked at 140C for onehour, yielding a primer layer composed of approximately 50 μg of EVAL.

A simulated reservoir layer was applied onto the primer layer, using thesame spraying technique, equipment, and formulation used for theapplying the primer. In this case, approximately 340 μg of wet coatingis applied, followed by drying, e.g., baking at 50C for about two hours,yielding about 300 μg of simulated drug-polymer reservoir layer.

A second composition can be prepared by mixing the following components:

-   (a) 2.0 mass % of Elast-Eon 80A and-   (b) the balance dimethylacetamide.

The second composition can be applied onto the dried simulated drugreservoir layer to form a topcoat layer. Using the same sprayingtechnique and equipment used for applying the simulated drug reservoirlayer. Approximately 340 μg of wet topcoat is applied followed by bakingat 80C for two hours, yielding a 300 μg Elast-Eon 80A topcoat layer.

Using a sliding wedge crimper, the stents were crimped onto 13 mm Tetracatheters (available from Guidant Corporation). The stents were expandedin deionized water at 37C with a balloon deployment pressure of 12 atm.Examination by SEM yielded FIGS. 1 & 2.

Example 2 Used to Make Stents for FIG. 3

A first composition was prepared by mixing the following component

-   (a) 4.0 mass % of poly(ethylene-co-vinyl alcohol) (EVAL) EC-151A and-   (b) the balance, an 80/20 weight blend of dimethylacetamide and    pentane.

The first composition was applied onto the surface of bare 13 mm TETRAstents (available from Guidant Corporation), which were firstpre-expanded by passing them over a 0.071 inch, tapered mandrel. Coatingwas sprayed and dried to form a primer layer. A spray coater was havinga 0.046 fan nozzle maintained at about 60C with a feed pressure 2.5 psi(0.17 atm) and an atomization pressure of about 15 psi (1.02 atm).Coating was applied at 10 μg per pass, in between which the stent wasdried for 10 seconds in a flowing air stream at 60C. Approximately 65 μgof wet coating was applied. The stents were baked at 140C for one hour,yielding a primer layer composed of approximately 60 μg of EVAL.

A simulated reservoir layer was applied onto the primer layer, using thesame spraying technique, equipment, and formulation used for theapplying the primer. In this case approximately 340 μg of wet coating isapplied, followed by drying, e.g., baking at 80C for about two hours,yielding about 315 μg of a simulated drug-polymer reservoir layer.

A second composition can be prepared by mixing the following components:

-   (a) 2.0 mass % of Solef 21508 and-   (b) the balance a 50/25/25, by weight, blend of acetone,    cyclohexanone, and AMS Defluxer.

AMS Defluxer is a blend of dichloropentafluoropropanes and methanolavailable from Tech Spray Inc. of Amarillo Tex.

The second composition can be applied onto the dried simulated drugreservoir layer to form a topcoat layer. Using the same sprayingtechnique and equipment used for applying the simulated drug reservoirlayer. Approximately 345 μg of wet topcoat is applied followed by bakingat 50C for two hours, yielding a 325 μg Solef 21508 topcoat layer.

Using a sliding wedge crimper, the stents were crimped onto 13 mm Tetracatheters (available from Guidant Corporation). After this, they weresubjected to a heat and pressure process wherein the balloon wasrestrained by a sheath, air pressure was applied to the catheter, andheat was applied to the balloon. Units were packaged and sterilized byelectron beam radiation at a dose of 35 KGy. The stent coatingperformance was evaluated in an apparatus where a guiding catheter wasconnected to flexible silicone tubing embedded in a block with threegradual 90-degree bends. Deionized water at 37C was recirculated throughthe guiding catheter. The stents were passed through a rotatinghemostatic valve attached to the guiding catheter, through the guidingcatheter, through the tortuous silicone tubing, and deployed at apressure of 12 atmospheres. After the stents were removed from thetubing, examination by SEM yielded FIGS. 3 & 4.

Appropriate standards for the measurement of durometer hardness are ASTMD2240 or ISO868.

While particular embodiments of the present invention have been shownand described, it will be obvious to those skilled in the art thatchanges and modifications can be made without departing from theembodiments of this invention in its broader aspects and, therefore, theappended claims are to encompass within their scope all such changes andmodifications as fall within the true spirit and scope of theembodiments of this invention. All patents, test procedures, and otherdocuments cited in this specification are fully incorporated byreference to the extent that this material is consistent with thisspecification and for all jurisdictions in which such incorporation ispermitted.

1. A method of making a medical device comprising a coated piece whereinthe coated piece comprises a coating, which optionally comprises apolymer or polymer combination and drug(s), wherein the methodcomprises: a) adjusting the temperature of the coating to a targettemperature followed by a crimping step; b) adjusting the temperature ofthe coating to a target temperature during a crimping step; c) adjustingthe temperature of the coating to a target temperature and maintainingthe temperature of the coating within plus or minus 5° C. of the targettemperature during a crimping step; d) adjusting the temperature of thecoating to a target temperature followed by crimping such that thetemperature of the coating remains within plus or minus 10° C. of thetarget temperature during a crimping step; or e) adjusting thetemperature of the coating to a temperature other than ambient towards atarget temperature and continuing to adjust the temperature of thecoating towards the target temperature during a crimping step.
 2. Themethod of claim 1 wherein the crimping step comprises the steps ofclosing the crimper, adjusting the temperature of the coating to asecond temperature, and opening the crimper wherein the secondtemperature is greater than or less than target temperature.
 3. Themethod of claim 1 wherein the device further comprises a catheter andwherein the crimping step attaches the coated piece to the catheter. 4.The method of claim 1 wherein the coating comprises a polymer or polymercombination.
 5. The method of claim 4 wherein the polymer or polymercombination comprises a polymer with Tg below ambient temperature. 6.The method of claim 4 wherein the polymer or polymer combinationcomprises a polymer with Tg above ambient temperature.
 7. The method ofclaim 4 wherein the polymer or polymer combination comprises a polymerthat is one of or any combination of poly(ester amides); ABS resins;acrylic polymers and acrylic copolymers; acrylonitrile-styrenecopolymers; alkyd resins; cellulose ethers; celluloses;copoly(ether-esters); copolymers of polycarboxylic acids andpoly-hydroxycarboxylic acids; copolymers of vinyl monomers with eachother and olefins; cyanoacrylates; epoxy resins; ethylene vinyl alcoholcopolymer; ethylene-α-olefin copolymers; ethylene-methyl methacrylatecopolymers; ethylene-vinyl acetate copolymers; poly(amino acids);poly(anhydrides); poly(imino carbonates); poly(iminocarbonate);poly(orthoesters); poly(tyrosine arylates); poly(tyrosine derivecarbonates); polyacrylates; polyacrylic acid; polyacrylic acids;polyacrylonitrile; polyalkylene oxalates; polyamides; polyamino acids;polyanhydride; polyanhydrides; polycarbonates; polycarboxylic acids;polycyanoacrylates; polyesters; polyethers; poly-hydroxycarboxylicacids; polyimides; polyisobutylene and ethylene-α-olefin copolymers;polyketones; polymethacrylates; polyolefins; polyorthoester;polyorthoesters; polyoxymethylenes; polyphosphazenes; polyphosphoester;polyphosphoester urethane; polyphosphoesters;polyphosphoesters-urethane; polyurethane; polyurethanes;poly(ether-urethanes), poly(ester-urethanes), poly(silicone-urethanes),polyvinyl alcohol; polyvinyl aromatics; polyvinyl esters; polyvinylethers; polyvinyl ketones; poly(vinylidene fluoride), poly(vinylidenechloride), poly(vinylidene fluoride-co-hexafluoropropene),poly(vinylidene fluoride-co-chlorotrifluoroethylene), poly(vinylfluoride), poly(vinyl chloride), polyvinylidene halides; silicones;starches; vinyl copolymers vinyl-olefin copolymers; vinyl halidepolymers and copolymers; and vinyl halide polymers vinyl halide polymerscopolymers
 8. The method of claim 4 wherein the polymer or polymercombination comprises a polymer that is one of or any combination ofstarch, sodium alginate, rayon-triacetate, rayon, polyvinylidenefluoride, polyvinylidene chloride, polyvinyl pyrrolidone, polyvinylmethyl ether, polyvinyl chloride, polyvinyl acetate, polystyrene,polyisocyanate, polyisobutylene, polyethylene glycol, polydioxanone,polycaprolactone, polycaprolactam, polyacrylonitrile, poly(trimethylenecarbonate), poly(L-lactic acid), poly(lactide-co-glycolide),poly(hydroxyvalerate), poly(hydroxybutyrate-co-valerate),poly(hydroxybutyrate-co-hydroxyvalerate), poly(hydroxybutyrate),poly(glycolide), poly(glycolic acid), poly(D,L-lactide-co-L-lactide),poly(D,L-lactide-co-glycolide), poly(D,L-lactide),poly(4-hydroxybutyrate), poly(3-hydroxybutyrate), poly(3-hydroxyvalerate), Nylon 66, hyaluronic acid, fibrinogen, fibrin,elastin-collagen, collagen, cellulose propionate, cellulose nitrate,cellulose butyrate, cellulose acetate butyrate, cellulose acetate,cellulose, cellophane, carboxymethyl cellulose, or poly(2-hydroxyethylmethacrylate).
 9. The method of claim 1 wherein the coated piece isselected from self-expandable stents, balloon-expandable stents, andstent-grafts.
 10. The method of claim 1 wherein the coating comprisesdrug(s) selected from antiproliferative, antineoplastic,antiinflammatory, antiplatelet, anticoagulant, antifibrin, antithrombin,antimitotic, antibiotic, antioxidants, or their combinations.
 11. Themethod of claims 1-10 wherein the target temperature is a) within orbelow the range defined by definition 1, definition 2, definition 3,definition 4, definition 5, definition 6, or definition 7 of the Tgrange of the polymer or polymer combination; b) within or above therange defined by definition 1, definition 2, definition 3, definition 4,definition 5, definition 6, or definition 7 of the Tg range of thepolymer or polymer combination; c) below ambient temperature; d) belowroom temperature; e) above ambient temperature; f) above roomtemperature; g) at or below −40° C.; h) between ambient temperature andupper Tg of the Tg range; i) between ambient temperature and lower Tg ofthe Tg range; j) between −40° C. and upper Tg of the Tg range; k)between −40° C. and lower Tg of the Tg range; l) between −40° C. andambient temperature; m) at or above 80° C.; n) between 80° C. and upperTg of the Tg range; o) between 80° C. and lower Tg of the Tg range; orp) between 80° C. and ambient temperature.
 12. The method of claim 11wherein the target temperature is limited to a temperature below thetemperature at which therapeutic agents present in the coatingsubstantially decompose.
 13. The method of claim 11 wherein the targettemperature is limited to a temperature below the temperature at whichdrug(s) present in the coating become substantially unsatisfactory fortheir intended use.
 14. The method of claim 11 wherein the targettemperature is chosen to simultaneously minimize deformation- anddelamination-based failure during crimping.
 15. The method of claim 11wherein Tg range of the polymer or polymer combination excludes ambienttemperature.
 16. The method of claim 11 wherein Tg range of the polymeror polymer combination excludes ambient temperature plus or minus 1° C.17. The method of claim 11 wherein Tg range of the polymer or polymercombination excludes ambient temperature plus or minus 5° C.
 18. Themethod of claim 11 wherein target temperature is chosen to yield achange in shore hardness wherein: a) the change is plus 50%; or b) thechange is minus 50%.
 19. The method of claim 18 wherein: a) the changeis plus 20%; or b) the change is minus 20%.
 20. The method of claim 11wherein the target temperature is a) for polymers which have a shorehardness of 60A to 80D; predominately exhibit deformation-based failuresduring crimping; have a Tg above room temperature; or have a Tg aboveambient temperature: i) within or below the range defined by definition1, definition 2, definition 3, definition 4, definition 5, definition 6,or definition 7 of the Tg range of the polymer or polymer combination;ii) below ambient temperature; iii) below room temperature; iv) at orbelow −40° C.; v) between ambient temperature and upper Tg of the Tgrange; vi) between ambient temperature and lower Tg of the Tg range;vii) between −40° C. and upper Tg of the Tg range; viii) between −40° C.and lower Tg of the Tg range; ix) between −40° C. and ambienttemperature; b) for polymers which have a shore hardness of 60D to 95D;predominately exhibit delamination-based failure during crimping; have aTg above room temperature; or have a Tg below ambient temperature: i)within or above the range defined by definition 1, definition 2,definition 3, definition 4, definition 5, definition 6, or definition 7of the Tg range of the polymer or polymer combination; ii) above ambienttemperature; iii) above room temperature; iv) at or above 80° C.; v)between 80° C. and upper Tg of the Tg range; vi) between 80° C. andupper Tg of the Tg range; vii) between 80° C. and lower Tg of the Tgrange; viii) between 80° C. and lower Tg of the Tg range; or ix) between80° C. and ambient temperature.
 21. The method of claim 20 wherein forpolymers that have a shore hardness of 60A to 80D the target temperatureis: a) within or below the range defined by definition 1, definition 2,definition 3, definition 4, definition 5, definition 6, or definition 7of the Tg range of the polymer or polymer combination; b) below ambienttemperature; c) below room temperature; d) at or below −40° C.; e)between ambient temperature and upper Tg of the Tg range; f) betweenambient temperature and lower Tg of the Tg range; g) between −40° C. andupper Tg of the Tg range; h) between −40° C. and lower Tg of the Tgrange; i) between −40° C. and ambient temperature;
 22. The method ofclaim 20 wherein for polymers that have a shore hardness of 60D to 95Dthe target temperature is: a) within or above the range defined bydefinition 1, definition 2, definition 3, definition 4, definition 5,definition 6, or definition 7 of the Tg range of the polymer or polymercombination; b) above ambient temperature; c) above room temperature; d)at or above 80° C.; e) between ambient temperature and upper Tg of theTg range; f) between ambient temperature and lower Tg of the Tg range;g) between 80° C. and upper Tg of the Tg range; h) between 80° C. andlower Tg of the Tg range; or i) between 80° C. and ambient temperature.23. The method of claim 20 wherein for polymers that predominatelyexhibit deformation-based failures during crimping the targettemperature is: a) within or below the range defined by definition 1,definition 2, definition 3, definition 4, definition 5, definition 6, ordefinition 7 of the Tg range of the polymer or polymer combination; b)below ambient temperature; c) below room temperature; d) at or below−40° C.; e) between ambient temperature and upper Tg of the Tg range; f)between ambient temperature and lower Tg of the Tg range; g) between−40° C. and upper Tg of the Tg range; h) between −40° C. and lower Tg ofthe Tg range; i) between −40° C. and ambient temperature;
 24. The methodof claim 20 wherein for polymers that predominately exhibitdelamination-based failure during crimping the target temperature is: a)within or above the range defined by definition 1, definition 2,definition 3, definition 4, definition 5, definition 6, or definition 7of the Tg range of the polymer or polymer combination; b) above ambienttemperature; c) above room temperature; d) at or above 80° C.; e)between ambient temperature and upper Tg of the Tg range; f) betweenambient temperature and lower Tg of the Tg range; g) between 80° C. andupper Tg of the Tg range; h) between 80° C. and lower Tg of the Tgrange; or i) between 80° C. and ambient temperature.
 25. The method ofclaim 20 wherein for polymers that have a Tg above room temperature thetarget temperature is: a) within or below the range defined bydefinition 1, definition 2, definition 3, definition 4, definition 5,definition 6, or definition 7 of the Tg range of the polymer or polymercombination; b) below ambient temperature; c) below room temperature; d)at or below −40° C.; e) between ambient temperature and upper Tg of theTg range; f) between ambient temperature and lower Tg of the Tg range;g) between −40° C. and upper Tg of the Tg range; h) between −40° C. andlower Tg of the Tg range; i) between −40° C. and ambient temperature;26. The method of claim 20 wherein for polymers that have a Tg aboveroom temperature the target temperature is: a) within or above the rangedefined by definition 1, definition 2, definition 3, definition 4,definition 5, definition 6, or definition 7 of the Tg range of thepolymer or polymer combination; b) above ambient temperature; c) aboveroom temperature; d) at or above 80° C.; e) between ambient temperatureand upper Tg of the Tg range; f) between ambient temperature and lowerTg of the Tg range; g) between 80° C. and upper Tg of the Tg range; h)between 80° C. and lower Tg of the Tg range; or i) between 80° C. andambient temperature.
 27. The method of claim 20 wherein for polymersthat have a Tg above ambient temperature the target temperature is: a)within or below the range defined by definition 1, definition 2,definition 3, definition 4, definition 5, definition 6, or definition 7of the Tg range of the polymer or polymer combination; b) below ambienttemperature; c) below room temperature; d) at or below −40° C.; e)between ambient temperature and upper Tg of the Tg range; f) betweenambient temperature and lower Tg of the Tg range; g) between −40° C. andupper Tg of the Tg range; h) between −40° C. and lower Tg of the Tgrange; i) between −40° C. and ambient temperature.
 28. The method ofclaim 20 wherein for polymers that have a Tg below ambient temperaturethe target temperature is: a) within or above the range defined bydefinition 1, definition 2, definition 3, definition 4, definition 5,definition 6, or definition 7 of the Tg range of the polymer or polymercombination; b) above ambient temperature; c) above room temperature; d)at or above 80° C.; e) between ambient temperature and upper Tg of theTg range; f) between ambient temperature and lower Tg of the Tg range;g) between 80° C. and upper Tg of the Tg range; h) between 80° C. andlower Tg of the Tg range; or i) between 80° C. and ambient temperature.29. The method of claim 20 wherein for polymers that have a shorehardness of 60A to 80D the target temperature is within or below therange defined by definition 1, definition 2, definition 3, definition 4,definition 5, definition 6, or definition 7 of the Tg range of thepolymer or polymer combination.
 30. The method of claim 20 wherein forpolymers that have a shore hardness of 60A to 80D the target temperatureis below ambient temperature.
 31. The method of claim 20 wherein forpolymers that have a shore hardness of 60A to 80D the target temperatureis at or below −40° C.
 32. The method of claim 20 wherein for polymersthat have a shore hardness of 60A to 80D the target temperature isbetween −40° C. and lower Tg of the Tg range.
 33. The method of claim 20wherein for polymers that have a shore hardness of 60D to 95D the targettemperature is within or above the range defined by definition 1,definition 2, definition 3, definition 4, definition 5, definition 6, ordefinition 7 of the Tg range of the polymer or polymer combination. 34.The method of claim 20 wherein for polymers that have a shore hardnessof 60D to 95D the target temperature is above ambient temperature. 35.The method of claim 20 wherein for polymers that have a shore hardnessof 60D to 95D the target temperature is at or above 80° C.
 36. Themethod of claim 20 wherein for polymers that have a shore hardness of60D to 95D the target temperature is between 80° C. and upper Tg of theTg range.
 37. The method of claim 20 wherein for polymers thatpredominately exhibit deformation-based failures during crimping thetarget temperature is within or below the range defined by definition 1,definition 2, definition 3, definition 4, definition 5, definition 6, ordefinition 7 of the Tg range of the polymer or polymer combination. 38.The method of claim 20 wherein for polymers that predominately exhibitdeformation-based failures during crimping the target temperature isbelow ambient temperature.
 39. The method of claim 20 wherein forpolymers that predominately exhibit deformation-based failures duringcrimping the target temperature is at or below −40° C.
 40. The method ofclaim 20 wherein for polymers that predominately exhibitdeformation-based failures during crimping the target temperature isbetween ambient temperature and upper Tg of the Tg range.
 41. The methodof claim 20 wherein for polymers that predominately exhibitdeformation-based failures during crimping the target temperature isbetween −40° C. and upper Tg of the Tg range.
 42. The method of claim 20wherein for polymers that predominately exhibit delamination-basedfailure during crimping the target temperature is within or above therange defined by definition 1, definition 2, definition 3, definition 4,definition 5, definition 6, or definition 7 of the Tg range of thepolymer or polymer combination.
 43. The method of claim 20 wherein forpolymers that predominately exhibit delamination-based failure duringcrimping the target temperature is above ambient temperature.
 44. Themethod of claim 20 wherein for polymers that predominately exhibitdelamination-based failure during crimping the target temperature is ator above 80° C.;
 45. The method of claim 20 wherein for polymers thatpredominately exhibit delamination-based failure during crimping thetarget temperature is between 80° C. and upper Tg of the Tg range. 46.The method of claim 20 wherein the target temperature is chosen tominimize deformation- or delamination-based failure during crimping. 47.The method of claim 46 wherein Tg range of the polymer or polymercombination excludes ambient temperature.
 48. The method of claim 46wherein Tg range of the polymer or polymer combination excludes ambienttemperature plus or minus 1° C.
 49. The method of claim 46 wherein Tgrange of the polymer or polymer combination excludes ambient temperatureplus or minus 5° C.
 50. The method of claim 46 wherein targettemperature is chosen to yield a change in shore hardness wherein: a)the change is plus 50%; or b) the change is minus 50%.
 51. The method ofclaim 50 wherein: a) the change is plus 20%; or b) the change is minus20%.
 52. The method of claim 11 wherein adjusting the temperaturecomprises disposing the coating or coated piece in thermal contact witha heat sink or heat source.
 53. The method of claim 52 wherein adjustingthe temperature comprises: a) thermally contacting the coating or coatedpiece with a heat sink or heat source; b) directing a heated or cooledgas at the coating or coated piece; c) placing the coating or coatedpiece near a heated or cooled surface for emitting thermal or infraredradiation to or absorbing thermal or infrared radiation from the coatingor coated piece; d) placing the coating or coated piece near a heated orcooled surface to enable convection to or from the coating or coatedpiece to the surface; e) i) heating or cooling the jaws of the crimper;and ii) thermally contacting the coating or coated piece with thecrimper jaws; f) for crimper jaws that allow the passage of infraredradiation, bathing the stent on catheter with infrared radiation; or g)heating the stent on catheter in an incubator or oven, or cooling thestent on catheter in a refrigerator to pre-equilibrate the stent oncatheter to the desired temperature before crimping.
 54. The method ofclaim 53 wherein adjusting the temperature comprises disposing thecoating or coated piece in thermal contact with a heat sink or heatsource.
 55. The device of claim 53 wherein the heat sink or heat sourceis integrated with a crimping device.
 56. The method of claim 21 whereinthe heat sink or heat source is integrated with a crimping device.
 57. Amethod of crimping a stent onto a delivery catheter or a balloon of thedelivery catheter comprising: a) positioning the stent on the catheteror the balloon; and b) crimping the stent on the catheter or a balloonwherein crimping is done at a target temperature, wherein the targettemperature is other than ambient temperature.
 58. The method of claim 1wherein the target temperature is a) within or below the range definedby definition 1, definition 2, definition 3, definition 4, definition 5,definition 6, or definition 7 of the Tg range of the polymer or polymercombination; b) within or above the range defined by definition 1,definition 2, definition 3, definition 4, definition 5, definition 6, ordefinition 7 of the Tg range of the polymer or polymer combination; c)below ambient temperature; d) below room temperature; e) above ambienttemperature; f) above room temperature; g) at or below −40° C.; h)between ambient temperature and upper Tg; i) between ambient temperatureand lower Tg; j) between −40° C. and upper Tg; k) between −40° C. andlower Tg; 1) between −40° C. and ambient temperature; m) at or above 80°C.; n) between 80° C. and upper Tg; o) between 80° C. and lower Tg; orp) between 80° C. and ambient temperature.
 59. The method of claim 58wherein the target temperature is a) for polymers which have a shorehardness of 60A to 80D; predominately exhibit deformation-based failuresduring crimping; have a Tg above room temperature; or have a Tg aboveambient temperature: i) within or below the range defined by definition1, definition 2, definition 3, definition 4, definition 5, definition 6,or definition 7 of the Tg range of the polymer or polymer combination;ii) below ambient temperature; iii) below room temperature; iv) at orbelow −40° C.; v) between ambient temperature and upper Tg; vi) betweenambient temperature and lower Tg; vii) between −40° C. and upper Tg;viii) between −40° C. and lower Tg; ix) between −40° C. and ambienttemperature; b) for polymers which have a shore hardness of 60D to 95D;predominately exhibits delamination-based failure during crimping; havea Tg above room temperature; or have a Tg below ambient temperature: i)within or above the range defined by definition 1, definition 2,definition 3, definition 4, definition 5, definition 6, or definition 7of the Tg range of the polymer or polymer combination; ii) above ambienttemperature; iii) above room temperature; iv) at or above 80° C.; v)between 80° C. and upper Tg; vi) between 80° C. and upper Tg; vii)between 80° C. and lower Tg; viii) between 80° C. and lower Tg; or ix)between 80° C. and ambient temperature.
 60. The method of claim 59wherein for polymers that have a shore hardness of 60A to 80D the targettemperature is: a) within or below the range defined by definition 1,definition 2, definition 3, definition 4, definition 5, definition 6, ordefinition 7 of the Tg range of the polymer or polymer combination; b)below ambient temperature; c) below room temperature; d) at or below−40° C.; e) between ambient temperature and upper Tg; f) between ambienttemperature and lower Tg; g) between −40° C. and upper Tg; h) between−40° C. and lower Tg; i) between −40° C. and ambient temperature; 61.The method of claim 59 wherein for polymers that have a shore hardnessof 60D to 95D the target temperature is: a) within or above the rangedefined by definition 1, definition 2, definition 3, definition 4,definition 5, definition 6, or definition 7 of the Tg range of thepolymer or polymer combination; b) above ambient temperature; c) aboveroom temperature; d) at or above 80° C.; e) between ambient temperatureand upper Tg; f) between ambient temperature and lower Tg g) between 80°C. and upper Tg; h) between 80° C. and lower Tg; or i) between 80° C.and ambient temperature.
 62. The method of claim 59 wherein for polymersthat predominately exhibit deformation-based failures during crimpingthe target temperature is: a) within or below the range defined bydefinition 1, definition 2, definition 3, definition 4, definition 5,definition 6, or definition 7 of the Tg range of the polymer or polymercombination; b) below ambient temperature; c) below room temperature; d)at or below −40° C.; e) between ambient temperature and upper Tg; f)between ambient temperature and lower Tg; g) between −40° C. and upperTg; between −40° C. and lower Tg; i) between −40° C. and ambienttemperature;
 63. The method of claim 59 wherein for polymers thatpredominately exhibit delamination-based failure during crimping thetarget temperature is: a) within or above the range defined bydefinition 1, definition 2, definition 3, definition 4, definition 5,definition 6, or definition 7 of the Tg range of the polymer or polymercombination; b) above ambient temperature; c) above room temperature; d)at or above 80° C.; e) between ambient temperature and upper Tg; f)between ambient temperature and lower Tg g) between 80° C. and upper Tg;h) between 80° C. and lower Tg; or i) between 80° C. and ambienttemperature.
 64. The method of claim 59 wherein for polymers that have aTg above room temperature the target temperature is: a) within or belowthe range defined by definition 1, definition 2, definition 3,definition 4, definition 5, definition 6, or definition 7 of the Tgrange of the polymer or polymer combination; b) below ambienttemperature; c) below room temperature; d) at or below −40° C.; e)between ambient temperature and upper Tg; f) between ambient temperatureand lower Tg; g) between −40° C. and upper Tg; h) between −40° C. andlower Tg; i) between −40° C. and ambient temperature;
 65. The method ofclaim 59 wherein for polymers that have a Tg above room temperature thetarget temperature is: a) within or above the range defined bydefinition 1, definition 2, definition 3, definition 4, definition 5,definition 6, or definition 7 of the Tg range of the polymer or polymercombination; b) above ambient temperature; c) above room temperature; d)at or above 80° C.; e) between ambient temperature and upper Tg; f)between ambient temperature and lower Tg g) between 80° C. and upper Tg;h) between 80° C. and lower Tg; or i) between 80° C. and ambienttemperature.
 66. The method of claim 59 wherein for polymers that have aTg above ambient temperature the target temperature is: a) within orbelow the range defined by definition 1, definition 2, definition 3,definition 4, definition 5, definition 6, or definition 7 of the Tgrange of the polymer or polymer combination; b) below ambienttemperature; c) below room temperature; d) at or below −40° C.; e)between ambient temperature and upper Tg; f) between ambient temperatureand lower Tg; g) between −40° C. and upper Tg; h) between −40° C. andlower Tg; i) between −40° C. and ambient temperature.
 67. The method ofclaim 59 wherein for polymers that have a Tg below ambient temperaturethe target temperature is: a) within or above the range defined bydefinition 1, definition 2, definition 3, definition 4, definition 5,definition 6, or definition 7 of the Tg range of the polymer or polymercombination; b) above ambient temperature; c) above room temperature; d)at or above 80° C.; e) between ambient temperature and upper Tg; f)between ambient temperature and lower Tg g) between 80° C. and upper Tg;h) between 80° C. and lower Tg; or i) between 80° C. and ambienttemperature.
 68. The method of claim 60-67 wherein the targettemperature is chosen to minimize deformation- or delamination-basedfailure during crimping.
 69. The method of claim 68 wherein Tg range ofthe polymer or polymer combination excludes ambient temperature plus orminus 5° C.
 70. The method of claim 68 wherein Tg range of the polymeror polymer combination excludes ambient temperature.
 71. The method ofclaim 68 wherein Tg range of the polymer or polymer combination excludesambient temperature plus or minus 1° C.
 72. The method of claim 68wherein target temperature is chosen to yield a change in shore hardnesswherein: a) the change is plus 50%; or b) the change is minus 50%. 73.The method of claim 68 wherein: a) the change is plus 20%; or b) thechange is minus 20%.
 74. A coating for a medical device made using themethod of claim
 11. 75. A device for crimping stents onto deliverycatheters or balloons that has a crimping means wherein the improvementcomprises a heating or cooling means integral with or adjacent to thecrimping means.